When our current grant on the control of cell division in psoriasis is up for competing renewal on May 1, 1975, it is proposed to expand the research into an interdisciplinary, interdependent program project on the pathogenesis and therapy of psoriasis. This program will combine the efforts of 14 investigators in six University departments: Dermatology, Biochemistry, Pharmacology, Pharmacy, Anatomy and Biostatistics. The program also includes six collaborators in the U.S.A. and one in Europe as well as multiple consultants here and elsewhere. The approaches involved will range from the cellular and molecular to the ultrastructural, immunological and clinical with extensive integration of these approaches. Major attention will be given to the following areas: The role of cyclic nucleotides (cyclic AMP, GMP and CMP) in the control of epidermal proliferation, differentiation and gene expression; possible immunological aberrations; the use of psoriatic skin transplanted to the "nude" mouse as an artificial animal model; glucocorticoid receptors in epidermis; epidermal cell culture, temperature sensitive epidermal variants, selection of hormone and cyclic nucleotide resistant epidermal cells; ultrastructural localization of the epidermal cyclic nucleotide system; pharmaceutical problems in delivery of cyclic nucleotide modulators into cells and clinical trials of cyclic nucleotide modulators. It is hoped that out of this interdisciplinary program will come a safe and efficacious therapy for the life-long control of psoriasis.